We performed RNA-sequencing analysis and precise bioinformatics analysis on 3 innate myeloid cell subsets, CD14-CD11c-, CD14-CD11c+, and CD14+CD11c+CD163low cells from NC and CDi.
Soluble CD14 is essential for lipopolysaccharide-dependent activation of human intestinal mast cells from macroscopically normal as well as Crohn's disease tissue.
Nineteen functional polymorphisms that alter the NFκB-mediated inflammatory response (TLR2 (rs3804099, rs11938228, rs1816702, rs4696480), TLR4 (rs5030728, rs1554973), TLR9 (rs187084, rs352139), LY96 (MD-2) (rs11465996), CD14 (rs2569190), MAP3K14 (NIK) (rs7222094)), TNF-α signaling (TNFA (TNF-α) (rs361525), TNFRSF1A (TNFR1) (rs4149570), TNFAIP3(A20) (rs6927172)) and other cytokines regulated by NFκB (IL1B (rs4848306), IL1RN (rs4251961), IL6 (rs10499563), IL17A (rs2275913), IFNG (rs2430561)) were associated with response to anti-TNF therapy among patients with CD, UC or both CD and UC (P ⩽ 0.05).
Although CD14 macrophages augment intestinal inflammation in patients with CD, macrophages also promote a negative feedback pathway through the activation of IL-22 production by RORγt ILCs.
Peripheral blood monocytes of patients with inactive CD showed normal expression of cell surface molecules (CD14, CD16, CD116), adherence to plastic surfaces, spontaneous migration, chemotaxis towards LTB4, phagocytosis of E. coli, and production of reactive oxygen species.
Polymorphisms in the CARD15/NOD2 gene, in addition to functional variants of the toll-like receptor-4 (TLR4) and CD14 genes, have been associated with the development of Crohn's disease.
In Korean population, the promoter polymorphism at -159 C/T of the CD14 gene is positively associated with IBD, both ulcerative colitis and Crohn's disease.
Importantly, lower expression of NFIL3 was observed in CD14(+) lamina propria mononuclear cells from Crohn's disease and ulcerative colitis patients compared with control subjects.
Genotype interaction analyses using three different statistical approaches provided significant evidence of interaction for the following combinations: CARD15/TLR4 (CD and UC), CARD15/CD14 (CD and UC), CD14/TLR4 (UC only), and CD14/BPI (UC only).
Primary (conventional, non-monocyte generated) CD1c(+)CD11c(+)CD14(-)CD16(-)CD19(-) myeloid blood or mucosal dendritic cells (mDC) from 76 patients with Crohn's disease (CD) or ulcerative colitis (UC) in remission, during flare-ups (FU) and 76 healthy or non-IBD controls were analysed by fluorescence activated cell sorter (FACS) flow cytometry and real-time polymerase chain reaction.
To examine whether TLR4 Asp299Gly, CD14-260C/T, TNF-1031T/C, TNF-863C/A, TNF-857C/T, TACE-172C/T, and TACE-154C/A polymorphisms are associated with Crohn disease in the Ashkenazi Jewish population, we analyzed families with at least 1 child with Crohn disease for association with these mutations using a family-based association test (transmission disequilibrium test) for analysis.
In the German cohort the CD14 single-nucleotide polymorphism was associated with UC, but not CD (UC p = 0.016 vs. CD p = 0.190), while the opposite was found in the Hungarian cohort (UC p = 0.083 vs. CD p = 0.019).
In further exploring the genetic background of these diseases, we investigated the variations in the CARD15/NOD2 gene (Arg702Trp, Gly908Arg and Leu1007fsinsC), and polymorphisms in the TLR4 gene (Asp299Gly and Thr399Ile) as well as in the promoter of the CD14 gene (T/C at position -159) in Greek patients with CD and UC.
In contrast, in patients with Crohn's disease there was no significant difference of the cumulative corticosteroid doses between the various T(-159)-->C promoter CD14 genotypes.
The genetic determination of the defense mechanisms in CD appears to be associated with the polymorphism of the Hsp70-2 gene rather than that of the CD14 or IL-10 genes.
In further exploring the genetic background of these diseases, we investigated the variations in the CARD15/NOD2 gene (Arg702Trp, Gly908Arg and Leu1007fsinsC), and polymorphisms in the TLR4 gene (Asp299Gly and Thr399Ile) as well as in the promoter of the CD14 gene (T/C at position -159) in Greek patients with CD and UC.
In summary, our findings provide evidence that the CARD15 3020insC risk allele influences disease susceptibility in a small proportion (<17%) of New Zealand CD patients, whereas there was no evidence that the CD14-159C/T polymorphism is associated with CD.
We could not replicate the described association between the CD14-159T allele and CD or UC, nor did we find any evidence for an interaction between the CARD15 or TNF-alpha risk alleles and the CD14-159T allele.